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| 1 | Efficient hepatic delivery and protein expression enabled by optimized mRNA and ionizable lipid nanoparticle显示文摘mRNA is a novel class of therapeutic modality that holds great promise in vaccination,protein replacement therapy,cancer immunotherapy,immune cell engineering etc.However,optimization of mRNA molecules and efficient in vivo delivery are quite important but challenging for its broad application.Here we present an ionizable lipid nanoparticle(iLNP)based on iBL0713 lipid for in vitro and in vivo expression of desired proteins using codon-optimized mRNAs.mRNAs encoding luciferase or erythropoietin(EPO)were prepared by in vitro transcription and formulated with proposed iLNP,to form iLP171/mRNA formulations.It was revealed that both luciferase and EPO proteins were successfully expressed by human hepatocellular carcinoma cells and hepatocytes.The maximum amount of protein expression was found at 6 h post-administration.The expression efficiency of EPO with codon-optimized mRNA was significantly higher than that of unoptimized mRNA.Moreover,no toxicity or immunogenicity was observed for these mRNA formulations.Therefore,our study provides a useful and promising platform for mRNA therapeutic development. | Tongren Yang Chunhui Li Xiaoxia Wang Deyao Zhao Mengjie Zhang Huiqing Cao Zicai Liang Haihua Xiao Xing-Jie Liang Yuhua Weng Yuanyu Huang | 2020 | Bioactive Materials2020,5,4: | 7 |
| 2 | Therapeutic siRNA:state of the art显示文摘RNA interference(RNAi)is an ancient biological mechanism used to defend against external invasion.It theoretically can silence any disease-related genes in a sequence-specific manner,making small interfering RNA(siRNA)a promising therapeutic modality.After a two-decade journey from its discovery,two approvals of siRNA therapeutics,ONPATTRO®(patisiran)and GIVLAARI™(givosiran),have been achieved by Alnylam Pharmaceuticals.Reviewing the long-term pharmaceutical history of human beings,siRNA therapy currently has set up an extraordinary milestone,as it has already changed and will continue to change the treatment and management of human diseases.It can be administered quarterly,even twice-yearly,to achieve therapeutic effects,which is not the case for small molecules and antibodies.The drug development process was extremely hard,aiming to surmount complex obstacles,such as how to efficiently and safely deliver siRNAs to desired tissues and cells and how to enhance the performance of siRNAs with respect to their activity,stability,specificity and potential off-target effects.In this review,the evolution of siRNA chemical modifications and their biomedical performance are comprehensively reviewed.All clinically explored and commercialized siRNA delivery platforms,including the GalNAc(N-acetylgalactosamine)–siRNA conjugate,and their fundamental design principles are thoroughly discussed.The latest progress in siRNA therapeutic development is also summarized.This review provides a comprehensive view and roadmap for general readers working in the field. | Bo Hu Liping Zhong Yuhua Weng Ling Peng Yuanyu Huang Yongxiang Zhao Xing-Jie Liang | 2020 | Signal Transduction and Targeted Therapy2020,5,1: | 4 |
| 3 | Advances of mRNA vaccines for COVID-19:A new prophylactic revolution begins显示文摘The world is in the midst of 2019 coronavirus infection disease(COVID-19)pandemic.As of 30 January 2021,more than 100 million cases and 2.1 million deaths were confirmed according to the data from the World Health Organization(WHO),resulting in a widespread social and economic turmoil.Therefore,researches worldwide are racing to deploy safe and effective COVID-19 vaccines. | Yuhua Weng Yuanyu Huang | 2021 | Asian Journal of Pharmaceutical Sciences2021,16,3: | 3 |
| 4 | ^(131)I-Evans blue: evaluation of necrosis targeting property and preliminary assessment of the mechanism in animal models显示文摘Necrosis is a form of cell death, which is related to various serious diseases such as cardiovascular disease, cancer, and neurodegeneration. Necrosis-avid agents(NAAs) selectively accumulated in the necrotic tissues can be used for imaging and/or therapy of related diseases. The aim of this study was to preliminarily investigate necrosis avidity of ^(131)I-evans blue( ^(131)I-EB) and its mechanism. The biodistribution of ^(131)I-EB at 24 h after intravenous administration showed that the radioactivity ratio of necrotic to viable tissue was 3.41 in the liver and 11.82 in the muscle as determined by γ counting in model rats. Autoradiography and histological staining displayed preferential uptake of ^(131)I-EB in necrotic tissues. In vitro nuclear extracts from necrotic cells exhibited 82.3% of the uptake in nuclei at 15 min, as well as 79.2% of the uptake at 2 h after ^(131)I-EB incubation. The DNA binding study demonstrated that evans blue(EB) has strong binding affinity with calf-thymus DNA(CT-DNA)(K_(sv)= 5.08×10~5 L/(mol/L)). Furthermore,the accumulation of ^(131)I-EB in necrotic muscle was efficiently blocked by an excess amount of unlabeled EB.In conclusion, ^(131)I-EB can not only detect necrosis by binding the DNA released from necrotic cells, but also image necrotic tissues generated from the disease clinically. | Qiaomei Jin Xin Shan Qi Luo Dongjian Zhang Yuanyu Zhao Nan Yao Fei Peng Dejian Huang Zhiqi Yin Wei Liu Jian Zhang | 2018 | Acta Pharmaceutica Sinica B2018,8,3: | 3 |
| 5 | Shear-responsive peptide/siRNA complexes as lung-targeting gene vectors显示文摘Particles administrated intravenously will pass through the pulmonary capillary network before being distributed to the body.Therefore,fabrication of vectors sensitive to blood shear and active with blood components should be a practical approach to develop lung-targe ting gene carriers self-regulated by circulatory system.In this work,we designed a series of cationic peptides with the same charge density but varying hydrophobicity and capacity to form hydrogen bonds,and investigated their ability to form co mplexes with siRNA,the behaviours of peptide/siRNA complexes in the presence of serum under shear,and the lung-targeting efficacy of the complexes regulated by blood.The hydrophobic interaction co ntrols the complexation between peptide and siRNA,while the hydrogen bonds are responsible for the binding of peptides to the serum components in blood.In vivo tests show that all the peptide/siRNA complexes can accumulate in lung.However,only the complexes that exhibit weak interaction with serum components and can be broken down by shear avoid the inflammation and death caused by pulmonary embolism.Moreover,the peptide with strong hydrophobicity can retain siRNA in lung without early release of the cargo.Our study provides a step toward the development of adaptive gene carriers under the regulation of circulatory system. | Dongxiao Yin Mengjie Zhang Jiaxin Chen Yuanyu Huang Dehai Liang | 2021 | Chinese Chemical Letters2021,32,5: | 2 |
| 6 | Advances of nanoparticles as drug delivery systems for disease diagnosis and treatment显示文摘Decades have passed since the first nanoparticles-base medicine was approved for human cancer treatment, and the research and development of nanoparticles for drug delivery are always undergoing.Nowadays, the significant advances complicate nanoparticles’ branches, including liposomes, solid lipid nanoparticles, inorganic nanoparticles, micelles, nanovaccines and nano-antibodies, etc. These nanoparticles show numerous capabilities in treatment and diagnosis of stubborn diseases like cancer and neurodegenerative diseases, emerging as novel drug carriers or therapeutic agents in future. In this review, the complicated branches of nanoparticles are classified and summarized, with their property and functions concluded. Besides, there are also some delivery strategies that make nanoparticles smarter and more efficient in drug delivery, and frontiers in these strategies are also summarized in this review. Except these excellent works in newly-produced drug delivery nanoparticles, some points of view and future expectations are made in the end. | Rui Liu Cong Luo Zhiqing Pang Jinming Zhang Shaobo Ruan Meiying Wu Lei Wang Tao Sun Nan Li Liang Han Jinjin Shi Yuanyu Huang Weisheng Guo Shaojun Peng Wenhu Zhou Huile Gao | 2023 | Chinese Chemical Letters2023,34,2: | 2 |
| 7 | Ionizable lipid-assisted efficient hepatic delivery of gene editing elements for oncotherapy显示文摘CRISPR/Cas9-based gene editing has emerged as a powerful biotechnological tool,that relies on Cas9 protein and single guided RNA(sgRNA)to edit target DNA.However,the lack of safe and efficient delivery carrier is one of the crucial factors restricting its clinical transformation.Here,we report an ionizable lipid nanoparticle(iLP181,pKa=6.43)based on iLY1809 lipid enabling robust gene editing in vitro and in vivo.The iLP181 effectively encapsulate psgPLK1,the best-performing plasmid expressing for both Cas9 protein and sgRNA targeting Polo-like kinase 1(PLK1).The iLP181/psgPLK1 nanoformulation showed uniformity in size,regular nanostructure and nearly neutral zeta potential at pH 7.4.The nanoformulation effectively triggered editing of PLK1 gene with more than 30%efficiency in HepG2-Luc cells.iLP181/psgPLK1 significantly accumulated in the tumor for more than 5 days after a single intravenous injection.In addition,it also achieved excellent tumor growth suppression compared to other nucleic acid modalities such as siRNA,without inducing adverse effects to the main organs including the liver and kidneys.This study not only provides a clinically-applicable lipid nanocarrier for delivering CRISPR/Cas system(even other bioactive molecules),but also constitutes a potential cancer treatment regimen base on DNA editing of oncogenes. | Chunhui Li Tongren Yang Yuhua Weng Mengjie Zhang Deyao Zhao Shuai Guo Bo Hu Wanxuan Shao Xiaoxia Wang Abid Hussain Xing-Jie Liang Yuanyu Huang | 2022 | Bioactive Materials2022,7,3: | 2 |
| 8 | Development and application of non-cir- cular gear emulsion motor显示文摘 | Xu Qin Huang Yuanyue | 2011 | Advanced Materials Research2011,,: | 1 |
| 9 | Antitumor synergism between PAK4 silencing and immunogenic phototherapy of engineered extracellular vesicles显示文摘Immunotherapy has revolutionized the landscape of cancer treatment.However,single immunotherapy only works well in a small subset of patients.Combined immunotherapy with antitumor synergism holds considerable potential to boost the therapeutic outcome.Nevertheless,the synergistic,additive or antagonistic antitumor effects of combined immunotherapies have been rarely explored.Herein,we established a novel combined cancer treatment modality by synergizing p21-activated kinase 4(PAK4)silencing with immunogenic phototherapy in engineered extracellular vesicles(EVs)that were fabricated by coating M1 macrophage-derived EVs on the surface of the nano-complex cores assembled with si RNA against PAK4 and a photoactivatable polyethyleneimine.The engineered EVs induced potent PAK4 silencing and robust immunogenic phototherapy,thus contributing to effective antitumor effects in vitro and in vivo.Moreover,the antitumor synergism of the combined treatment was quantitatively determined by the Compu Syn method.The combination index(CI)and isobologram results confirmed that there was an antitumor synergism for the combined treatment.Furthermore,the dose reduction index(DRI)showed favorable dose reduction,revealing lower toxicity and higher biocompatibility of the engineered EVs.Collectively,the study presents a synergistically potentiated cancer treatment modality by combining PAK4 silencing with immunogenic phototherapy in engineered EVs,which is promising for boosting the therapeutic outcome of cancer immunotherapy. | Mei Lu Haonan Xing Wanxuan Shao Pengfei Wu Yuchuan Fan Huining He Stefan Barth Aiping Zheng Xing-Jie Liang Yuanyu Huang | 2023 | Acta Pharmaceutica Sinica B2023,13,9: | 1 |
| 10 | An Efficient and High-Throughput Electroporation Microehip Applicable for siRNA Delivery 显示文摘 | Huang Huang Zewen Wei Yuanyu Huang | 2011 | Lab on a Chip2011,11,: | 1 |
| 11 | Biosafety materials:Ushering in a new era of infectious disease diagnosis and treatment with the CRISPR/Cas system显示文摘Despite multiple virus outbreaks over the past decade,including the devastating coronavirus disease 2019(COVID-19)pandemic,the lack of accurate and timely diagnosis and treatment technologies has wreaked havoc on global biosecurity.The clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated proteins(Cas)system has the potential to address these critical needs for tackling infectious diseases to detect viral nucleic acids and inhibit viral replication.This review summarizes how the CRISPR/Cas system is being utilized for the treatment and diagnosis of infectious diseases with the help of biosafety materials and highlights the design principle and in vivo and in vitro efficacy of advanced biosafety materials used to deal with virus attacks. | Yuquan Zhang Ziyue Li Julien Milon Essola Kun Ge Xuyan Dai Huining He Haihua Xiao Yuhua Weng Yuanyu Huang | 2022 | Biosafety and Health2022,4,2: | 1 |
| 12 | siRNA-functionalized lanthanide nanoparticle enables efficient endosomal escape and cancer treatment显示文摘Attaching DNA/RNA to nanomaterials is the basis for nucleic acid-based assembly and drug delivery.Herein,we report that small interfering RNA(siRNA)effectively coordinates with ligand-free lanthanide nanoparticles(NaGdF4 NPs),and forms siRNA/NaGdF4 spherical nucleic acids(SNA).The coordination is primarily attributed to the interaction between Gd and phosphate backbone of the siRNA.Surprisingly,an efficient encapsulation and rapid endosomal escape of siRNA from the endosome/lysosome were achieved,due to its flexible ability to bound to phospholipid head of endosomal membrane,thereby disrupting the membrane structure.Resorting to the dual properties of NaGdF4 NPs,siRNA loading,and endosomal escape,siRNA targeting programmed cell death-ligand 1(siPD-L1)/NaGdF4 SNA triggers significant gene silencing in vitro and in vivo,and effectively represses the tumor growth in both CT26 tumor model and 4T1 orthotopic murine model. | Chanchan Yu Kun Li Lin Xu Bo Li Chunhui Li Shuai Guo Ziyue Li Yuquan Zhang Abid Hussain Hong Tan Mengyu Zhang Yongxiang Zhao Yuanyu Huang Xing-Jie Liang | 2022 | Nano Research2022,15,10: | 1 |
| 13 | Ionizable liposomal siRNA therapeutics enables potent and persistent treatment of Hepatitis B显示文摘Small interfering RNA(siRNA)constitutes a promising therapeutic modality supporting the potential functional cure of hepatitis B.A novel ionizable lipidoid nanoparticle(RBP131)and a state-of-the-art lyophilization technology were developed in this study,enabling to deliver siRNA targeting apolipoprotein B(APOB)into the hepatocytes with an ED_(50)of 0.05 mg/kg after intravenous injection.In addition,according to the requirements of Investigational New Drug(IND)application,a potent siRNA targeting hepatitis B virus(HBV)was selected and encapsulated with RBP131 to fabricate a therapeutic formulation termed RB-HBV008. | Yuanyu Huang Shuquan Zheng Zhaoxu Guo Xavier de Mollerat du Jeu Xing-Jie Liang Zhiwei Yang Hong-Yan Zhang Shan Gao Zicai Liang | 2022 | Signal Transduction and Targeted Therapy2022,7,3: | 1 |
| 14 | The microgravity enhanced polymer-mediated siRNA gene silence by improving cellular uptake显示文摘Microgravity(MG)effect is a weightlessness phenomenon caused by the distance from the ground or low gravity of other planets outside the earth's atmosphere.The various effects of MG have been corroborated in human and animal studies and modeled in cell-based analogs.However,the impact of MG on siRNA performance remains to be elucidated,which is crucial for aerospace medicine.In this study,we prepared nucleic acid nanomicelles(EAASc/siRNA)by using tri-block copolymer of PEG45-PAMA40-P(C7A36-DBA37)(EAASc)and siRNA and explored its working mechanism under simulated microgravity(SMG)condition generated by a random positioning machine(RPM).The binding ability of EAASc to siRNA and silence activity were firstly confirmed in normal gravity(NG)environment.Evaluation of PLK1 mRNA expression revealed that gene inhibition efficiencies were increased by 28.7%(HepG2)and 28.9%(A549)under SMG condition,compared with those under NG condition.In addition,mechanism exploration indicated that morphology and migration capability of cancer cells were significantly changed,the internalization of EAASc/siRNA by cells was magnified when the cells were incubated with RPM.No significant difference was observed regarding the expression profiles of genes involved in RNA interference(RNAi)pathway,including Ago2,Dicer,TRBP,and so on.Taken together,siRNA activity was elevated under SMG condition owning to increased cellular internalization.This study,for the first time to our knowledge,provides valuable theory for development and application of siRNA therapeutic in space in the future. | Tongren Yang Chanchan Yu Changrong Wang Chunhui Li Mengjie Zhang Xiaofan Luo Yuhua Weng Anjie Dong Xiaoqiong Li Yulin Deng Yuanyu Huang | 2020 | Biophysics Reports2020,6,6: | 1 |
| 15 | Lipid-conjugated siRNA hitchhikes endogenous albumin for tumor immunotherapy显示文摘With the development of a small interfering RNA(siRNA)delivery strategy,increasing siRNA therapeutics for tumor treatment appeared in clinical trials and pre-clinical development.However,the test results of such therapeutics unveiled that efficient siRNA delivery to tumor tissues is still challenging.Albumin is considered an ideal carrier for delivering hydrophobic agents into tumor tissue because it is highly concentrated and long-circulating in blood and has propensity of tumor enrichment.Herein,we synthesized lipid conjugated siRNAs(LsiRNAs),which showed high affinity to albumin.Mechanistically,LsiRNAs non-covalently bind to the hydrophobic core of albumin through its octadecyl tails.The small size of albumin/LsiRNAs allows the complex to penetrate tumor tissue efficiently.Biodistribution test proved that albumin extremely prolonged circulation time and increased tumor retention of associated LsiRNAs.Notably,LsiRNA against programmed death ligand-1(Pdl1)efficiently suppressed tumor growth as well as prolonged survival time of tumor bearing mice by increasing infiltration of CD8^(+)T cells as well as promoted the maturation of dendritic cells both in tumor and lymph.Together,LsiRNAs provide a simple but effective way for siRNA tumor delivery that“hitchhikes”on albumin. | Bo Hu Sudong Kong Yuhua Weng Deyao Zhao Abid Hussain Qingze Jiao Shijing Zhan Ling Qiu Jianguo Lin Minhao Xie Bo Li Yuanyu Huang | 2023 | Chinese Chemical Letters2023,34,11: | 0 |
| 16 | Synergistic optimization of electrical and thermal transport in n-type Bi-doped PbTe by introducing coherent nanophase Cu1-75Te显示文摘Based on the calculated results of band structures and density of states,Bi doping is used to adjust its carrier concentration in order to obtain n-type PbTe materials with high power factor.Then,coherent nanophase Cu1.75Te is in situ formed in the n-type PbTe matrix,which can simultaneously optimize the thermal and electrical properties.As a result,at a relative lower temperature than other reports,the highest ZT value of 1.4 is obtained at 623 K for the nominal Pb0995Bi0005Te+0.86 wt%Cu175Te sample.More importantly,the ZT hold a higher value in the broad temperature;especially,ZT value is about 1.2-1.4 in the temperature range of 573-773 K,which is beneficial to the significant average ZT value ZTave~0.9 in the temperature range of 300-773 K.These results indicate that it is an effective and feasible method to enhance the thermoelectric properties via synergistic modulation of electrical and thermal transport properties by element doping and in situ coherent nanophase. | Chen Zhu Jian Zhang Hongwei Ming Lulu Huang Yuanyue Li Tao Chen Di Li Baoli Zhang Jingtao Xu Xiaoying Qin | 2021 | Journal of Materiomics2021,7,1: | 0 |
| 17 | Vacuolar Phosphate Transporter1 (VPT1) may transport sugar in response to soluble sugar status of grape fruits显示文摘Vacuolar Phosphate Transporter1(VPT1)-mediated phosphate uptake in the vacuoles is essential to plant development and fruit ripening.Interestingly,here we find that the VPT1 may transport sugar in response to soluble sugar status of fruits.The VvVPT1 protein isolated from grape(Vitis vinifera)berrieswas tonoplast-localized and contains SPX(Syg1/Pho81/XPR1)and MFS(major facilitator superfamily)domains.Its mRNA expression was significantly increased during fruit ripening and induced by sucrose.Functional analyses based on transient transgenic systems in grape berry showed that VvVPT1 positively regulated berry ripening and significantly affected hexose contents,fruit firmness,and ripening-related gene expression.The VPT1 proteins(Grape VvVPT1,strawberry FaVPT1,and Arabidopsis AtVPT1)all showed low affinity for phosphate verified in yeast system,while they appear different in sugar transport capacity,consistent with fruit sugar status.Thus,our findings reveal a role for VPT1 in fruit ripening,associated to its SPX and MFS domains in direct transport of soluble sugar available into the vacuole,and open potential avenues for genetic improvement in fleshy fruit. | Qian Bai Xuexue Chen Zhenzhen Zheng Jinjing Feng Yanjun Zhang Yuanyue Shen Yun Huang | 2023 | Horticulture Research2023,10,2: | 0 |
| 18 | Recent progresses of exosome-liposome fusions in drug delivery显示文摘Exosomes are membrane-bound nanoscale extracellular vesicles,which produced by almost all organisms.Due to the excellent biocompatibility,long circulation time as well as low immunogenicity,exosomes as naturally-derived drug delivery carriers have experienced explosive growth over the past decades.However,issues such as insufficient loading efficiency,heterogeneous delivery efficiency,uncontrollable targeting ability,and low production limit their wide application.Recently,the emerging exosome-liposome fusion strategy has become a potential approach to solve such issues.Thus,this review mainly focuses on the currently developed exosome-liposome fusion strategy and their application in drug delivery as well as disease treatment.This review aims to shed light on the advantages of fusion strategy in drug delivery and provides a better understanding for more rational design.The current challenge and future perspective regarding their clinical translation and application will also be discussed. | Lulu Zheng Bo Hu Deyao Zhao Wenjing Liu Qing Liu Yuanyu Huang Shaobo Ruan | 2024 | Chinese Chemical Letters2024,35,2: | 0 |
| 19 | Combination of XianGui capsule and LCZ696 inhibits doxorubicin- induced heart failure in mice显示文摘Objective:We used doxorubicin(DOX)-induced heart failure mouse model to investigate the therapeutic effect and involved mechanism of XianGui capsule(XG)combined with Sacubitril Valsartan Sodium tablets(LCZ696)on heart failure.Methods:C57BL/6 mice were divided into control(Ctrl)group,DOX group,XG group,LCZ696 group and combination(XL)group.After the administration,mice heart functions,blood pressure,and serum cardiac injury markers were detected.Heart sections were conducted with HE,Sirius Red and immunohistochemical staining.The heart tissues were collected for the determination of protein or mRNA expression of anti oxidative,fibrosis,inflammation and apoptosis-related genes by Western Blot and qRT-PCR.Results:XG,LCZ696 or XG plus LCZ696 can significantly improve the heart functions of mice,reduce the expression of cardiac injury markers,and inhibit myocardial fibrosis.Mechanically,XG,LCZ696 or their co treatment antagonized myocardial apoptosis,increase forkhead box O3a,superoxide dismutase 2(SOD2)protein,SOD1,catalase mRNA expressions and inhibited the protein and mRNA levels of toll-like 4,nuclear factorkB,and inflammatory cytokines.Conclusion:XG,LCZ696 or XG plus LCZ696 decreases DOX-induced cardiomyocytes apoptosis by reducing inflammatory factors and enhancing expression of antioxidant enzymes,thereby alleviating the development of heart failure. | Yuanyu Wang Rong Huang Jihong Han Xiaoxiao Yang Yajun Duan | 2021 | TMR Modern Herbal Medicine2021,4,3: | 0 |
| 20 | pH-Responsive polymer boosts cytosolic siRNA release for retinal neovascularization therapy显示文摘Small interfering RNA(siRNA)has a promising future in the treatment of ocular diseases due to its high efficiency,specificity,and low toxicity in inhibiting the expression of target genes and proteins.However,due to the unique anatomical structure of the eye and various barriers,delivering nucleic acids to the retina remains a significant challenge.In this study,we rationally design PACD,an A-B-C type non-viral vector copolymer composed of a hydrophilic PEG block(A),a siRNA binding block(B)and a pH-responsive block(C).PACDs can self-assemble into nanosized polymeric micelles that compact siRNAs into polyplexes through simple mixing.By evaluating its pH-responsive activity,gene silencing efficiency in retinal cells,intraocular distribution,and anti-angiogenesis therapy in a mouse model of hypoxia-induced angiogenesis,we demonstrate the efficiency and safety of PACD in delivering siRNA in the retina.We are surprised to discover that,the PACD/siRNA polyplexes exhibit remarkable intracellular endosomal escape efficiency,excellent gene silencing,and inhibit retinal angiogenesis.Our study provides design guidance for developing efficient nonviral ocular nucleic acid delivery systems. | Shuai Guo Chunhui Li Changrong Wang Xiaowen Cao Xinyue Liu Xing-Jie Liang Yuanyu Huang Yuhua Weng | 2024 | Acta Pharmaceutica Sinica B2024,14,2: | 0 |